Cocaine exposure in fetal rhesus monkey: consequences for dopamine D1- and D2-like receptor binding densities.
Previously we found that dopamine D1-, D2- and D5-receptor mRNA subtypes are significantly increased in the rostral forebrain of fetal monkeys exposed to cocaine. The purpose of the present study was to determine whether cocaine exposure during gestation also increases dopamine receptor binding densities in the fetal brain. Pregnant monkeys were treated with cocaine (3 mg/kg, i.m., n = 3) or physiological saline (n = 3), 4 times per day from day 22 of pregnancy until day 70. Quantitative receptor autoradiography of dopamine D1-like receptors was performed on day-70 fetal brain sections using [3H]SCH23390. [3H]Spiperone was used to characterize dopamine D2-like receptors. Image analysis of receptor autoradiograms revealed a high-density dopamine D1-like receptor binding in the striatum, nucleus accumbens (ACB) and the substantia nigra (SN), whereas lower binding densities were observed in the frontal cortex and the habenula (Hb). Dopamine D2-like receptor binding was also found in the frontal cortex, striatum and ACB, but was not detected in the Hb or SN. The pattern of dopamine receptor distribution was the same in both control and cocaine-treated animals. However, there was a significant increase in the density of sites for D1-like receptors in the striatum (P < 0.05) and SN (P < 0.01) and for D2-like receptors in the striatum (P < 0.01) of cocaine-treated animals versus saline-treated controls. These findings suggest that D1- and D2-like receptors are present in dopamine target neurons, whereas D2-like autoreceptors can not be detected in day-70 fetal monkey midbrain. The present results provide further support for the hypothesis that gestational cocaine exposure causes reduced synthesis and release of dopamine which leads to dopamine D1- and D2-receptor up-regulation in dopamine target neurons.
Fang
Y
Y
Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland 97201, USA.
Janowsky
A
A
Rønnekleiv
O K
OK
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000196:embryology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D008253:Macaca mulatta; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis*; D017447:Receptors, Dopamine D1 / Q000235:genetics* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D003042:Cocaine